ABSTRACT Many patients with debilitating hearing loss have notable hearing asymmetry. When a large asymmetry exists between ears, attempts to fit bilateral amplification can be problematic. If one ear has moderate hearing loss and one ear has severe to profound hearing loss, patients often discontinue amplification in the poor ear, due to limited benefit. Consequently, they listen with only one ear, which receives an impoverished signal caused by the hearing loss. Without bilateral input, there is little support for binaural hearing advantages. For these individuals, the only available treatment that can provide hearing to the poor ear is a cochlear implant (CI). Treatment with a CI in the poor ear and a hearing aid (HA) in the contralateral better ear would allow for bilateral input and potentially provide binaural hearing benefits. Unfortunately, these patients are not routinely implanted in the deaf ear because the contralateral ear has moderate rather than severe to profound hearing loss. A longitudinal prospective, single-arm, multi-center clinical trial that addresses the effects of asymmetric hearing loss in various listening contexts and evaluates potential treatment with a CI is critically needed. Findings from the proposed study will also guide a future Phase III clinical trial. In Aim 1, preliminary efficacy data is obtained in adults with asymmetric hearing loss who receive a CI in the poor ear and maintain a HA in the better ear. To evaluate the effects of treatment to the poor ear, word recognition and sound audibility with a CI are compared to pre-implant performance with a HA. Aim 2 evaluates effectiveness of bimodal hearing in this population; bimodal refers to use of a CI in the poor ear while maintaining a HA in the better ear. Measures are sound localization in quiet and noise, speech recognition in noise, and speech recognition at soft presentation levels. Post-implant bimodal performance is compared to the best aided pre-implant performance. The protocol will include characterization and quantification of asymmetric hearing loss effects and subsequent treatment as perceived by the individual and the individual's spouse/significant other. Quality of Life metrics address general health, communication function, hearing disability/handicap, social and emotional consequences of hearing loss, and post-treatment satisfaction and perceived benefit. Aim 2 also collects essential preliminary information related to patient selection, recruitment, test measures, methodology, data management and assurance of data quality to be used in the development of a future Phase III clinical trial. The protocol's clinical utility, including efficiency of administration, ease of interpretation, and applicability to clinical decision making across multiple sites will be determined. In summary, the results of the proposed study could profoundly influence the direction of clinical decisions and treatment for a substantial patient population who must rely on a unilateral signal that is degraded by hearing loss.